The objective of this investigation will be to determine the central nervous system membrane alterations produced by acute and chronic ethanol and barbiturate administration which occur in a correlative manner to the development of tolerance and physical dependence to these drugs. Specifically, male Sprague-Dawley rats will be separated into five treatment groups (control, acute, tolerant, withdrawn, and recovered). Whole brains and brain regions (cortex, basal ganglia, limbic system, reticular formation, hypothalamus, and cerebellum) will be removed from animals in each of these treatment groups and synaptosomes, synaptosomal plasma (SPM), mitochondria, and microsomes will be isolated by ultracentrifugation. Whole brains, brain regions, and the membrane fractions (synaptosomes, SPM, etc.) from whole brains and brain regions will be analyzed for ethanol or barbiturate-induced changes in membrane phospholipid (individual phospholipids to be measured include phosphatidic acid, phosphatidycholine, phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine) and cholesterol content. In addition, ethanol and/or barbiturate-medi*ted changes in membrane calcium content will be measured by atomic absorption spectrometry. Changes in synaptosomal membrane calcium influx and efflux after acute and chronic ethanol and barbiturate treatment will also be examined subsequent to KC1 depolarization (71 mM KC1) and addition of the calcium ionophore A23187 (10 micromoles). Finally, the ability of ethanol and barbiturates to depress energy-dependent accumulation of calcium by microsomes and mitochondria will be examined to determine the effects of acute and chronic administration of these drugs on ATP-dependent processes. This proposed investigation will delineate those membrane alterations involving calcium and membrane lipids which result from acute and chronic ethanol or barbiturate treatment. In addition, brain regions where effects are most predominant will be demonstrated along with differential influence of ethanol and barbiturates.